Amphiphilic Block Copolymer Poly Research Articles

Nitric oxide producing artificial enzymes based on metalloporphyrins

Artificial enzymes are synthetic materials or molecules that exhibit enzyme-like activities. Herein, we report artificial enzymes based on metalloporphyrins (MPs) that can mimic nitric oxide synthase (NOS) to produce nitric oxide (NO) from l-arginine (Arg) using hydrogen peroxide (H2O2) as an oxidant, and we determine the microenvironmental influence on their activity and stability. An assortment of structurally diverse water-soluble MPs was synthesized, and their NO production was compared. Improved catalytic activity and stability of the lead MP were observed when it was conjugated to the hydrophilic homopolymer poly(2-carboxyethyl acrylate) (PCEA). Micelles assembled from the amphiphilic block copolymer poly(cholesteryl methacrylate)-block-PCEA functionalized with the lead MP, and MP-conjugated PCEA polymer chains immobilized on silica particles resulted in moieties with ∼3× higher catalytic activity compared to the monomeric MP. Finally, the PCEA-coated silica particles could use the MPs as motor units to exhibit enhanced diffusion in the presence of the required fuel molecules Arg and H2O2. Taken together, the microenvironments of the artificial enzymes have a marked impact on their activity and stability, and these NO-producing MPs offer an interesting synthetic alternative to their natural counterparts.

Polymer Micelles vs Polymer-Lipid Hybrid Vesicles: A Comparison Using RAW 264.7 Cells.

Bottom-up synthetic biology aims to integrate artificial moieties with living cells and tissues. Here, two types of structural scaffolds for artificial organelles were compared in terms of their ability to interact with macrophage-like murine RAW 264.7 cells. The amphiphilic block copolymer poly(cholesteryl methacrylate)-block-poly(2-carboxyethyl acrylate) was used to assemble micelles and polymer–lipid hybrid vesicles together with 1,2-dioleoyl-sn-glycero-3-phosphocholine or 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) lipids in the latter case. In addition, the pH-sensitive fusogenic peptide GALA was conjugated to the carriers to improve their lysosomal escape ability. All assemblies had low short-term toxicity toward macrophage-like murine RAW 264.7 cells, and the cells internalized both the micelles and hybrid vesicles within 24 h. Assemblies containing DOPE lipids or GALA in their building blocks could escape the lysosomes. However, the intracellular retention of the building blocks was only a few hours in all the cases. Taken together, the provided comparison between two types of potential scaffolds for artificial organelles lays out the fundamental understanding required to advance soft material-based assemblies as intracellular nanoreactors.

Design and development of DSPC:DAP:PDMAEMA-b-PLMA nanostructures: from the adumbration of their morphological characteristics to in vitro evaluation

In this study, 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC), 1,2-dioleoyl-3-dimethylammonium-propane (DAP) and amphiphilic block copolymer poly(2-(dimethylamino)ethyl methacrylate)-b-poly(lauryl methacrylate) (PLMA-b-PDMAEMA) in the weight ratios: 1:0:0.03, 1:0.1:0.03, 1:0.3:0.03, 1:0.5:0.03, 1:0.7:0.03, and1:1:0.03, were used for the design and development of hybrid polymer-lipid nanostructures. The polymer-lipid nanostructures were prepared using the aqueous heat method. The pure lipid systems were used as reference systems. Differential Scanning Calorimetry (DSC) was utilized to investigate the interactions between the components. The presence of the polymeric guest caused different orientation of the polar groups of phospholipids, as the DSC thermotropic values revealed. The changes of the physicochemical characteristics of the systems with the increase of the weight ratio of DAP are more intense in comparison to those without this lipid due to the presence of the block copolymer, which contributes significantly to the repulsive interactions between the vesicles as a result of its positive charge. The only exception is the DSPC:DAP:PLMA-b-PDMAEMA nanosystem at 1:0.5:0.03 wt ratio, where the size of the polymer/lipid structures (Dh≈320 nm) increased and the ζ-potential decreased in absolute values in comparison with the systems with lower weight ratio of the DAP lipid. Cryogenic Transmission Electron Microscopy (cryo-TEM) images showed different structures which strongly depend on the composition of the system, ranging from lamella structures, disc forms, and “spaghetti” morphologies. Based on toxicity studies, it was found all samples are biocompatible and show a dose-dependent cytotoxicity on HEK293 (Human Embryonic Kidney 293 cell line). In conclusion, we developed polymer/lipid nanostructures with knowledge of their structural and physicochemical characteristics, useful as drug or antigen delivery platforms.

Self-Assembled Nanosized Vehicles from Amino Acid-Based Amphiphilic Polymers with Pendent Carboxyl Groups for Efficient Drug Delivery.

Developing safe and efficient delivery vehicles for chemotherapeutic drugs has been a long-standing demanding. Amino acid-based polymers are promising candidates to address this challenge due to their excellent biocompatibility and biodegradation. Herein, a series of well-defined amphiphilic block copolymers were prepared by PET-RAFT polymerization of N-acryloyl amino acid monomers. By altering monomer types and the block ratio of the copolymers, the copolymers self-assembled into nanostructures with various morphologies, including spheres, rod-like, fibers, and lamellae via hydrophobic and hydrogen bonding interactions. Significantly, the nanoparticles (NPs) assembled from amphiphilic block copolymers poly(N-acryloyl-valine)-b-poly(N-acryloyl-aspartic acid) (PV-b-PD) displayed an appealing cargo loading efficiency (21.8-32.6%) for a broad range of drugs (paclitaxel, doxorubicin (DOX), cisplatin, etc.) due to strong interactions. The DOX-loaded PV-b-PD NPs exhibited rapid cellular uptake (within 1 min) and a great therapeutic performance. These drug delivery systems provide new insights for regulating the controlled morphologies and improving the efficiency of drug delivery.

Evaluation of Hybrid Vesicles in an Intestinal Cell Model Based on Structured Paper Chips.

Cell culture-based intestinal models are important to evaluate nanoformulations intended for oral drug delivery. We report the use of a floating structured paper chip as a scaffold for Caco-2 cells and HT29-MTX-E12 cells that are two established cell types used in intestinal cell models. The formation of cell monolayers for both mono- and cocultures in the paper chip are confirmed and the level of formed cell-cell junctions is evaluated. Further, cocultures show first mucus formation between 6-10 days with the mucus becoming more pronounced after 19 days. Hybrid vesicles (HVs) made from phospholipids and the amphiphilic block copolymer poly(cholesteryl methacrylate)-block-poly(2-carboxyethyl acrylate) in different ratios are used as a representative soft nanoparticle to assess their mucopenetration ability in paper chip-based cell cultures. The HV assembly is characterized, and it is illustrated that these HVs cross the mucus layer and are found intracellularly within 3 h when the cells are grown in the paper chips. Taken together, the moist three-dimensional cellulose environment of structured paper chips offers an interesting cell culture-based intestinal model that can be further integrated with fluidic systems or online read-out opportunities.

Ratiometric fluorescent chemosensor based on the block copolymer of poly(N‐isopropylacrylamide)‐b‐poly(N‐vinylcarbazole) containing rhodamine 6G and 1,8‐naphthalimide moieties

AbstractWe have synthesized an amphiphilic block copolymer poly(N‐isopropylacrylamide)‐b‐poly(N‐vinylcarbazole) containing 1,8‐naphthalimide and spirolactam rhodamine 6G moieties via reversible addition‐fragmentation chain transfer radical polymerization. The photoluminescence (PL) spectrum of the poly(N‐vinylcarbazole) block well matches the absorption spectrum of the 1,8‐naphthalimide moiety and the enhanced emission with a peak at 510 nm from the 1,8‐naphthalimide moiety is found in the block copolymer film for excitation at 330 nm. The 560‐nm emission from the rhodamine 6G moiety is observed as the block copolymer film sprayed by Britton‐Robinson (B‐R) buffers or Fe3+ aqueous solutions for excitation at 330 and 400 nm. The PL intensity at 560 nm is markedly increased for the pH value of the B‐R buffer lower than 3.0 or the Fe3+ concentration in water higher than 5 × 10−4 M. The 560‐nm PL intensity is much higher for the block copolymer film photoexcited at 330 nm than that photoexcited at 400 nm due to double‐step resonance energy transfer. The PL intensity ratio of 560 to 510 nm (I560/I510) is dependent on the resonance energy transfer from 1,8‐naphthalimide to rhodamine 6G, which is sensitive to the concentrations of H+ and Fe3+ ions in water.

Hypoxia/Temperature/pH Triple Stimuli–Responsive Block Copolymers: Synthesis, Self‐Assembly, and Controlled Drug Release

AbstractThe amphiphilic block copolymer poly(methacrylic acid‐co‐2‐nitroimidazole acrylate)‐b‐poly(2‐(N,N‐dimethylamino)ethyl methacrylate) (P(MAA‐co‐NIMA)‐b‐PDMAEMA) with the hypoxia/temperature/pH triple responsiveness is synthesized by reversible addition‐fragmentation chain transfer polymerization (RAFT), hydrolysis, and 3‐(3‐dimethylaminopropyl)‐1‐ethylcarbodiimide (EDC) reactions, and successfully self‐assembled into micelles. The hypoxia response in vitro is realized, and then the sensitivity of the self‐assembled micelles to the hypoxia condition is studied by controlling the grafting amount of aminated 2‐nitroimidazole. Because 2‐(N,N‐dimethylamino) ethyl methacrylate (DMAEMA) is a typical material sensitive to temperature and pH conditions, the self‐assembled micelles are also responsive to temperature and different acidic/basic conditions. In addition, the cumulative release rate of doxorubicin (DOX) at 42 °C, pH = 6.0, and hypoxic conditions increases significantly, and verifies the synergistic promotion effect of the above stimulations. This intelligent polymer with triple response mechanism improves the controllability and efficiency of drug release, and is expected to be a drug carrier for cancer treatment.

Association of the Thermodynamics with the Functionality of Thermoresponsive Chimeric Nanosystems.

Stimuli-responsive nanosystems are an emerging technology in the field of therapy and are very promising for various applications, including targeted drug delivery. In this chapter, our scope is to integrate two different methodologies, namely differential scanning calorimetry (DSC) and dynamic light scattering (DLS), in order to rationally approach the functional behavior of thermoresponsive chimeric/mixed liposomes and interpret their thermoresponsiveness on a thermodynamic basis. In particular, chimeric bilayers comprised of the phospholipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) and two different-in-composition thermoresponsive amphiphilic block copolymers poly(N-isopropylacrylamide)-b-poly(lauryl acrylate) (PNIPAM-b-PLA) 1 or 2 were built by a conventional evaporation technique, followed by DSC, and chimeric liposomes of DPPC and PNIPAM-b-PLA 1 were developed and studied by DLS, after preparation and after a simple heating protocol. The results from both methodologies indicate the composition- and concentration-dependent lyotropic effect of the foreign copolymer molecule on the properties and functionality of the lipidic membrane.

Preparation of poly( o ‐phenylenediamine) nanoparticles with hydrolysed PEO 45 ‐ b ‐P t BA 35 as template and its electrochemical properties

Amphiphilic block copolymer poly(ethylene oxide)-b-poly(tert-butyl acrylate) (PEO45-b-PtBA35) from atom transfer radical polymerisation was hydrolysed to varying degrees through adjusting hydrolysis time. And the hydrolysis product poly(ethylene oxide)-b-poly(acrylic acid) (PEO45-b-PAA35) was obtained and used as a template to synthesise nanostructured poly(o-phenylenediamine) (PoPD). The influence of hydrolysis degrees of PEO45-b-PAA35 on the size and electrochemical properties of PoPD was investigated. Results showed that the PoPD particles have uniform sizes, and their size could be tuned with the hydrolysis degree of PEO45-b-PAA35. The average diameter and length of PoPD were less than 86 and 135 nm, and the size of these particles was increased with the increase of hydrolysis degree of PEO45-b-PAA35. Electrochemical characterisation proves that the particle with a smaller size had a better electrochemical activity. When the hydrolysis time was 12 h, the PoPD had the best specific capacitance compared with other samples. The discharge specific capacitance calculated by chronopotentiometric test of this sample is reached 809 F·g−1 at the current density of 0.5 A·g−1.

Functionalization of electrospun PLA fibers using amphiphilic block copolymers for use in carboxy-methyl-cellulose hydrogel composites

Carboxy-methyl-cellulose (CMC) hydrogels, prepared in the presence of a crosslinker and photoinitiator, were reinforced with 3.7 wt% electrospun PLA fibers to create CMC hydrogel composites. To improve fiber-matrix adhesion, electrospun fiber mats based on hybrids of PLA and amphiphilic block copolymer (BCP) poly(D,L-lactide)-block-poly[2-(dimethylamino)ethyl methacrylate] (PLA-b-PDMAEMA) were produced. The presence of PDMAEMA at the fiber surface induced hydrophilic surface properties, which could be controlled by varying the PDMAEMA chain length. PDMAEMA was quaternized and co-electrospun with PLA fibers, which further enhanced the interaction between fibers and hydrogel matrix via ionic interactions. Physicochemical properties of the electrospun fiber mats and their CMC hydrogel based composites were assessed and revealed a nearly two orders of magnitude increase in modulus. Continuous electrospun fiber mats were chopped into discontinuous fibers to create short fiber reinforced CMC hydrogels. Rheological properties of these reinforced hydrogels incorporating 0.5 wt% discontinuous fibers were evaluated and showed potential as injectable composite systems for biomedical applications.

Novel pH-Sensitive Urushiol-Loaded Polymeric Micelles for Enhanced Anticancer Activity.

PurposeThe aim of this study was to develop a means of improving the bioavailability and anticancer activity of urushiol by developing an urushiol-loaded novel tumor-targeted micelle delivery system based on amphiphilic block copolymer poly(ethylene glycol)-b-poly-(β-amino ester) (mPEG-PBAE).Materials and MethodsWe synthesized four different mPEG-PBAE copolymers using mPEG-NH2 with different molecular weights or hydrophobicity levels. Of these, we selected the mPEG5000-PBAE-C12 polymer and used it to develop an optimized means of preparing urushiol-loaded micelles. Response surface methodology was used to optimize this formulation process. The micellar properties, including particle size, pH sensitivity, drug release dynamics, and critical micelle concentrations, were characterized. We further used the MCF-7 human breast cancer cell line to explore the cytotoxicity of these micelles in vitro and assessed their pharmacokinetics, tissue distribution, and antitumor activity in vivo.ResultsThe resulting micelles had a mean particle size of 160.1 nm, a DL value of 23.45%, and an EE value of 80.68%. These micelles were found to release their contents in a pH-sensitive manner in vitro, with drug release being significantly accelerated at pH 5.0 (98.74% in 72 h) without any associated burst release. We found that urushiol-loaded micelles were significantly better at inducing MCF-7 cell cytotoxicity compared with free urushiol, with an IC50 of 1.21 mg/L. When these micelles were administered to tumor model animals in vivo, pharmacokinetic analysis revealed that the total AUC and MRT of these micelles were 2.28- and 2.53-fold higher than that of free urushiol, respectively. Tissue distribution analyses further revealed these micelles to mediate significantly enhanced tumor urushiol accumulation.ConclusionThe pH-responsive urushiol-loaded micelles described in this study may be ideally suited for clinical use for the treatment of breast cancer.

Architecture based selectivity of Amphiphilic block copolymers of poly(ethylene oxide) and poly(ε-caprolactone) for drug delivery

Architecture of amphiphilic block copolymers is an important parameter that affects their critical micelles concentration (CMC), drug loading capacity and drug release behavior. In this context, 4-arm star-shaped block copolymers comprising of poly(ethylene oxide) as a hydrophilic segment and poly(ε-caprolactone) as a hydrophobic part, 4 s-P(CL-b-EO), is compared with its linear counterpart having otherwise similar total molar mass, chemical composition and molar mass of individual components (PCL-b-PEO-b-PCL). As a first step, the micelles prepared by linear block copolymer (LPM) and star-shaped block copolymer (SPM) were compared for CMC, drug encapsulation capacity, and drug release behavior. Micelles based on star-shaped polymers were found to have low CMC, high drug encapsulation capacity and better sustained release behavior. Blood hemolysis and cytotoxicity studies of both linear and star-shaped block copolymers revealed that these are safer to use for biological applications. Micelles based on star shaped polymers (SPM) and linear block copolymer (LPM) were further employed for individual delivery of cefixime (CEF) and its co-delivery with clarithromycin (CLA). Finally, growth inhibition efficiency of SPM, LPM, CEF, CLA, CEF-SPM, CEF-LPM, CEF-CLA-SPM, and CEF-CLA-LPM are evaluated against S. pneumoniae and S. pneumoniae (resistant) by antibacterial assay and morphological topography imaging by AFM. Minimum inhibitory concentration (MIC50) of drugs encapsulated in SPM is found to be considerably lower compared to direct application of drugs and drug encapsulated in LPM.

Cell-Penetrating, Peptide-Based RAFT Agent for Constructing Penetration Enhancers.

Peptide-polymer conjugates represent a promising class of compounds that can be used to overcome some of the limitations associated with peptides intended for therapeutic and diagnostic applications. The efficient generation of well-defined peptide/protein-polymer conjugates can promote the development of the design and synthesis of functional drugs and gene delivery platforms. In this research, a sequence defined cell penetrating peptide (i.e., Transportan 10 (TP 10))-based chain transfer agent (TP-CTA) was designed and synthesized in an automated peptide synthesizer. Thereafter, amphiphilic block copolymers poly[oligo(ethylene glycol) methyl ether acrylate]-b-poly(n-butyl acrylate) (TP-POEGA-b-PBA) were synthesized using the TP-CTA via reversible addition-fragmentation chain transfer (RAFT) polymerization. Circular dichroism (CD) spectroscopy confirmed the preservation of α-helix structure of TP 10, which is crucial for its bioactivity. Transmission electron microscopy (TEM) revealed the formation of self-assembled rod-like and vesicle nanostructures in an aqueous environment. Finally, the obtained peptide-conjugated block copolymers were demonstrated to be effective compounds for cell penetration. This method opens up a way for accessing peptide-polymer conjugates with cell-penetrating abilities.

Luminescent core–shell nanoparticles with crosslinked aggregation‐induced emission core structures: Emission both in solution and solid states

AbstractLuminescent core–shell nanoparticles (NPs) with crosslinked aggregation‐induced emission (AIE) core structures, which exhibited excellent emission independent of the dispersion state of the NPs, have been developed by a facile one‐pot method based on the self‐assembly of an amphiphilic block copolymer poly(PEGMA)‐b‐poly(DB3VT). Core–shell micelles with a poly(DB3VT) core were formed from poly(PEGMA)‐b‐poly(DB3VT) in tetrahydrofuran (THF)/H2O condition, and the crosslinked AIE‐based structure was selectively incorporated into the core by the Suzuki coupling reaction between poly(DB3VT) blocks and tetraphenylethylene (TPE)‐based coupling monomers at the same time. This method afforded a uniform NP with a crosslinked TPE‐based AIE core structure. The obtained NP exhibited excellent emission both in diluted solution and solid states. This result indicated that the formed TPE‐based AIE core structure was always aggregated regardless of NP dispersion owing to the crosslinking as we expected. The crosslinked TPE‐based AIE core structure, which was related to the emission property, was readily tuned by the selection and combination of coupling monomers in the Suzuki coupling reaction. By incorporating electron‐deficient units into the core, the emission color could be successfully tuned from yellow‐green to orange and red while maintaining the emission property independent of the state of the NP dispersion. These results demonstrated that NPs with the crosslinked AIE core structures are a promising luminescent material design motif to realize emission independent on molecular dispersion.

Two-Way CO2-Responsive Polymer Particles with Controllable Amphiphilic Properties.

Multiple stimuli-responsive amphiphilic block copolymers of poly(methacrylic acid) (PMAA) and poly(2-dimethylaminoethyl methacrylate) (PDMAEMA) were used as emulsifiers to prepare two-way CO2 stimuli-responsive poly(methyl methacrylate) (PMMA) latex particles via aqueous emulsion polymerization. The polymerization at pH 2 and 50 °C produced mainly PDMAEMA-surfaced PMMA latex particles, whereas the polymerization at pH 12 and 50 °C produced mainly PMAA-surfaced particles. Both types of latex particles appeared to precipitate at higher pH values from the emulsifier of a longer PDMAEMA block length. The direction from precipitation to dispersion for PDMAEMA-surfaced particles or from dispersion to precipitation for PMAA-surfaced particles in response to CO2 bubbling of the pH 12 dispersion of particles depended on the PDMAEMA block length. Together, this study reveals that—by tuning the PDMAEMA block length in PMAA-b-PDMAEMA used as an emulsifier and polymerization at pH 2 or 12—PMMA latex particles can exhibit two-way CO2 responsiveness between dispersion and precipitation. Thus, due to their simple preparation and unique dual pH and CO2 responsiveness, these newly developed PMAA-b-PDMAEMA emulsifiers provide a highly efficient approach for the development of smart PMMA latex nanoparticles with desirable multifunctional properties.

Self-assembly of amphiphilic poly(styrene-b-acrylic acid) on magnetic latex particles and their application as a reusable scale inhibitor.

The deposition of scale on membranes or container and pipe surfaces (clogging the system) is a costly issue in water treatment processes or water-cooling systems. To effectively cope with this issue, magnetic polymeric nanoparticles (MPNPs) have been developed and applied as promising scale inhibitors, due to their high surface-area-to-volume ratio, surface modifiability, and magnetic separation ability. Carboxylated MPNPs, having a monodisperse size distribution (236 ± 26 nm) with a high magnetic content of 70 wt% and superparamagnetic properties, were fabricated by using a 2-step process: (i) formation of clusters of hydrophobic magnetic nanoparticles stabilized by oleic acid (OA-MNPs), and (ii) self-assembly of the amphiphilic block copolymer of poly(styrene27-b-acrylic acid120) (PS27-b-PAA120) onto the cluster surfaces. With application of ultrasonication to 12.0 wt% OA-MNPs, a three-dimensional network was formed by particle–particle interactions, suppressing coalescence, and then creating stable magnetic clusters. The cluster surfaces were then adsorbed by amphiphilic PS27-b-PAA120via the attractive force between hydrophobic PS blocks. This moves longer hydrophilic PAA blocks containing carboxylic acid groups into the water phase. The formulated MPNPs acted as a nanosorbent for calcium ion (Ca2+) removal with a removal efficiency of 92%. The MPNPs can be effectively reused for up to 4 cycles. Based on the electrostatic interactions between the negatively-charged polymer and the hydrated Ca2+, the resulting precipitation leads to the prevention of calcium carbonate scale formation. Insights into this mechanism open up a new perspective for magnetic-material applications as effective antiscalants.

Synthesis and self-assembly of poly(ethylene glycol)-block-poly(N-3-(methylthio)propyl glycine) and their oxidation-sensitive polymersomes

Amphiphilic block copolymers poly(ethylene glycol)-block-poly(N-3-(methylthio)propyl glycine) (PEG-b-PMeSPG) were synthesized via ring-opening polymerization of N-3-(methylthio)propyl glycine N-thiocarboxyanhydride (MeSPG-NTA) initiated by amino-terminated PEG. The self-assemblies of three PEG-b-PMeSPG copolymers with different PMeSPG block lengths were first prepared by nanoprecipitation method using THF and DMF, respectively, as the organic solvent, and their morphologies were studied by Cryo-EM and DLS. To prepare polymersomes loaded with glucose oxidase (GOx), double emulsion method followed by extrusion treatment was employed. The oxidation-responsive disruption of polymersomes was achieved upon the introduction of glucose because of the oxidants generated in-situ by GOx/glucose.

Mesoscale Simulations of pH-Responsive Amphiphilic Polymeric Micelles for Oral Drug Delivery.

It is of great significance to study the structure property and self-assembly of amphiphilic block copolymer in order to effectively and efficiently design and prepare drug delivery systems. In this work, dissipative particle dynamics (DPD) simulation method was used to investigate the structure property and self-assembly ability of pH-responsive amphiphilic block copolymer poly(methyl methacrylate-co-methacrylic acid)-b-poly(aminoethyl methacrylate) (poly(MMA-co-MAA)-b-PAEMA). The effects of different block ratios (hydrophilic PAEMA segment and pH-sensitive PMAA segment) in copolymer on self-assembly and drug loading capacity including drug distribution were extensively investigated. The increase of hydrophilic PAEMA facilitated the formation of a typical core-shell structure as well as a hydrophobic PMAA segment. Furthermore, the optimal drug-carrier ratio was confirmed by an analysis of the drug distribution during the self-assembly process of block copolymer and model drug Ibuprofen (IBU). In addition, the drug distribution and nanostructure of IBU-loaded polymeric micelles (PMs) self-assembled from precise block copolymer (PMMA-b-PMAA-b-PAEMA) and block copolymer (poly(MMA-co-MAA)-b-PAEMA) with random pH-responsive/hydrophobic structure were evaluated, showing that almost all drug molecules were encapsulated into a core for a random copolymer compared to the analogue. The nanostructures of IBU-loaded PMs at different pH values were evaluated. The results displayed that the nanostructure was stable at pH < pKa and anomalous at pH > pKa which indicated drug release, suggesting that the PMs could be used in oral drug delivery. These findings proved that the amphiphilic block copolymer P(MMA30-co-MAA33)-b-PAEMA38 with random structure and pH-sensitivity might be a potential drug carrier. Moreover, DPD simulation shows potential to study the structure property of PMs self-assembled from amphiphilic block copolymer.

Synthesis of poly(sodium styrene sulfonate)-b-poly(butyl acrylate) block copolymers via RAFT emulsifier-free emulsion polymerization and their application in PEDOT aqueous dispersions

The amphiphilic block copolymers of poly(sodium styrene sulfonate)-b-poly(butyl acrylate) (PSS-b-PBA) with different block molar ratios were synthesized via RAFT surfactant-free emulsion polymerization. Poly(3,4-ethylenedioxythiophene) aqueous dispersions (PEDOT:PSS-b-PBA) were prepared with PSS-b-PBA block copolymers as the templates. The composition and performance of PSS-b-PBA and PEDOT:PSS-b-PBA were investigated. Results showed that the amphiphilic PSS-b-PBA block copolymers were successfully synthesized via RAFT surfactant-free emulsion polymerization in a controlled way and the composition of the block copolymers were confirmed by Nuclear Magnetic Resonance (NMR) spectrum and Thermogravimetric Analysis (TGA). PSS-b-PBA block copolymers formed micelles in aqueous matrix and the critical micelle concentrations (cmc) were found to be around 10−6 g mL−1, which were determined by fluorescence spectrometry method. The stable PEDOT aqueous dispersions were fabricated using the amphiphilic PSS-b-PBA block copolymers as the templates. The block molar ratio of the block copolymers had little effects on the polymerization kinetics of EDOT. But the conductivity of the PEDOT film was greatly enhanced when the block copolymers were used as the templates, which was supposed to be caused by the core-shell structure of the block copolymers.

Stimuli-Responsive Lyotropic Liquid Crystalline Nanosystems with Incorporated Poly(2-Dimethylamino Ethyl Methacrylate)-b-Poly(Lauryl Methacrylate) Amphiphilic Block Copolymer.

There is an emerging need to evolve the conventional lyotropic liquid crystalline nanoparticles to advanced stimuli-responsive, therapeutic nanosystems with upgraded functionality. Towards this effort, typically used stabilizers, such as Pluronics®, can be combined or replaced by smart, stimuli-responsive block copolymers. The aim of this study is to incorporate the stimuli-responsive amphiphilic block copolymer poly(2-(dimethylamino)ethyl methacrylate)-b-poly(lauryl methacrylate) (PDMAEMA-b-PLMA) as a stabilizer in lipidic liquid crystalline nanoparticles, in order to provide steric stabilization and simultaneous stimuli-responsiveness. The physicochemical and morphological characteristics of the prepared nanosystems were investigated by light scattering techniques, cryogenic-transmission electron microscopy (cryo-TEM), X-ray diffraction (XRD) and fluorescence spectroscopy. The PDMAEMA-b-PLMA, either individually or combined with Poloxamer 407, exhibited different modes of stabilization depending on the lipid used. Due to the protonation ability of PDMAEMA blocks in acidic pH, the nanoparticles exhibited high positive charge, as well as pH-responsive charge conversion, which can be exploited towards pharmaceutical applications. The ionic strength, temperature and serum proteins influenced the physicochemical behavior of the nanoparticles, while the polymer concentration differentiated their morphology; their micropolarity and microfluidity were also evaluated. The proposed liquid crystalline nanosystems can be considered as novel and attractive pH-responsive drug and gene delivery nanocarriers due to their polycationic content.